DK200101919A - Bone marrow specific protein - Google Patents

Description

SEQUENCE LISTING <110> Human Genome Sciences, Inc. <120> Bone Marrow-Specific Protein

<130> PF495.PCT <140> Unassigned <141> 2000-01-13 <150> 60 / 116,236 <151> 1999-01-15 <160> 23 <170> Patent Vern. 2.1 <210> 1 <211> 485

<212> DNA <213> Homo sapiens <22 0> <221> CDS <222> (62) .. (367) <400> 1 agattcacgc accctcaaga gtgtgggtga gacatataca gcctgttaga cctgaaggca 60 g atg get one aag gcc aat aag hole etc to tcc gca gga ttg aag 109 Met Ala Leu Leu Lys Ala Asn Lys Asp Leu Ile Ser Ala Gly Leu Lys 15 10 15 gag ttc age gtt ctg ctg aat cag cag gtc ttc aat hole cct etc gtc 157

Glu Phe Ser Val Leu Asn Gin Gin Val Phe Asn Asp Pro Leu Val 20 25 30 tet gaa gaa gac atg gtg act gtg gtg gag gac tgg atg aac ttc tac 205

Ser Glu Glu Asp With Val Thr Val Val Glu Asp Trp With Asn Phe Tyr 35 40 45 ate aac tat tac agg cag cag gtg aca ggg gag ccc caa gag ega gac 253

Ile Asn Tyr Tyr Arg Gin Gin Val Thr Gly Glu Pro Gin Glu Arg Asp 50 55 60 aag get ctg cag gag et egg caa gag ctg aac act ctg gcc aac cct 301

List Ala Leu Gin Glu Leu Arg Gin Glu Leu Asn Thr Leu Ala Asn Pro 65 70 75 80 ttc ctg gcc aag tac agg gac ttc ctg aag tet cat gag etc ccg agt 349

Phe Leu Ala Lys Tyr Arg Asp Phe Leu Lys Ser His Glu Leu Pro Ser 85 90 95 cac cca ccg ccc tcc tcc tagctcaggg acccagcccc tcctctctga 397

His Pro Pro Pro Ser Ser 100 gaaactctga ccttcatgtc cttaggctgt gctcctgcca ctctaccctg acacctcaat 457 aaagaccagt gctggttttg ttggaaaa 485

<210> 2 <211> 102 <212> PRT <213> Homo sapiens <400> 2

With Ala Leu Leu List Ala Asn List Asp Leu Ile Ser Ala Gly Leu List 15 10 15

Glu Phe Ser Val Leu Asn Gin Gin Val Phe Asn Asp Pro Leu Val 20 25 30

Ser Glu Glu Asp With Val Thr Val Val Glu Asp Trp With Asn Phe Tyr 35 40 45

Ile Asn Tyr Tyr Arg Gin Gin Val Thr Gly Glu Pro Gin Glu Arg Asp 50 55 50

List Ala Leu Gin Glu Leu Arg Gin Glu Leu Asn Thr Leu Ala Asn Pro 65 70 75 80

Phe Leu Ala Lys Tyr Arg Asp Phe Leu Lys Ser His Glu Leu Pro Ser 85 90 95

His Pro Pro Pro Ser Ser 100

<210> 3 <211> 102 <212> PRT <213> Homo sapiens <400> 3

With Ala Pro Phe Gin Ser Asn List Asp Leu Ile Ser Thr Gly Ile List 15 10 15

Glu Phe Asn Val Leu Asp Gin Gin Val Phe Asp Asp Pro Leu Ile 20 25 30

Ser Glu Glu Asp With Val Ile Val Val His Asp Trp Val Asn Leu Tyr 35 40 45

Thr Asn Tyr Tyr Light Light Leu Val His Gly Glu Gin Glu Glu Gin Asp 50 55 60

Arg Ala With Thr Glu Phe Gin Gin Glu Leu Ser Thr Leu Gly Ser Gin 65 70 75 80

Phe Leu Ala Lys Tyr Arg Thr Phe Leu Lys Ser Lys Glu Pro Pro Ser 85 90 95

Asn Thr Leu Pro Ser Ser 100 <210> 4 <211> 36

<212> DNA <213> Homo sapiens <400> 4 ctgcagccat ggctcttctt aaggccaata aggatc 36 <210> 5 <211> 37

<212> DNA <213> Homo sapiens <400> 5 tctcccaagc ttttaggagg agggcggtgg gtgactc 37

<210> 6 <211> 42 <212> DNA <213> Homo sapiens <400> 6 ctacgcggat ccgccatcat ggctcttctt aaggccaata ag 42

<210> 7 <211> 33 <212> DNA <213> Homo sapiens <400> 7 ctctgctcta gactaggagg agggcggtgg gtg 33 <210> 8 <211> 42

<212> DNA <213> Homo sapiens <400> 8 gcagcaggat ccgccatcat ggctcttctt aaggccaata ag 42

<210> 9 <211> 30 <212> DNA <213> Homo sapiens <400> 9 gcagcaggta ccggaggagg gcggtgggtg 30

<210> 10 <211> 733 <212> DNA <213> Homo sapiens <400> 10 gggatccgga gcccaaatct tctgacaaaa ctcacacatg cccaccgtgc ccagcacctg 60 aattcgaggg tgcaccgtca gtcttcctct tccccccaaa acccaaggac accctcatga 120 tctcccggac tcctgaggtc acatgcgtgg tggtggacgt aagccacgaa gaccctgagg 180 tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca aagccgcggg 240 aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg caccaggact 300 ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca acccccatcg 360 agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac accctgcccc 420 catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc aaaggcttct 480 atccaagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac aactacaaga 540 ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag ctcaccgtgg 500 acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat gaggctctgc 660 acaaccacta cacgcagaag agcctctccc tgtctccggg taaatgagtg cgacggccgc 720 gactctagag hole 733 <210> 11 <211> 86 <212> DNA <213> Homo sapiens <400> 11 gcgcctcgag atttccccga aatctag that tccccgaaat gatttccccg aaatgatttc 60 cccgaaatat ctgccatctc aattag 86 <210> 12 <211> 27

<212> DNA <213> Homo sapiens <400> 12 gcggcaagct ttttgcaaag cctaggc 27 <210> 13 <211> 271

<212> DNA <213> Homo sapiens <400> 13 ctcgagattt ccccgaaatc tagatttccc cgaaatgatt tccccgaaat gatttccccg 60 aaatatctgc catctcaatt agtcagcaac catagtcccg cccctaactc cgcccatccc 120 gcccctaact ccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat 180 ttatgcagag gccgaggccg cctcggcctc tgagctattc cagaagtagt gaggaggctt 240 ttttggaggc ctaggctttt gcaaaaagct t 271 <210> 14 <211> 32

<212> DNA <213> Homo sapiens <400> 14 gcgctcgagg gatgacagcg atagaacccc gg 32

<210> 15 <211> 31 <212> DNA <213> Homo sapiens <400> 15 gcgaagcttc gcgactcccc ggatccgcct c 31

<210> 16 <211> 12 <212> DNA <213> Homo sapiens <400> 16 ggggactttc cc 12

<210> 17 <211> 73 <212> DNA <213> Homo sapiens <400> 17 gcggcctcga ggggactttc ccggggactt tccggggact ttccgggact ttccatcctg 60 ccatctcaat tag 73 <210> 18 <211> 27

<212> DNA <213> Homo sapiens <400> 18 gcggcaagct ttttgcaaag cctaggc 27

<210> 19 <211> 256 <212> DNA <213> Homo sapiens <400> 19 ctcgagggga ctttcccggg gactttccgg ggactttccg ggactttcca tctgccatct 60 caattagtca gcaaccatag tcccgcccct aactccgccc atcccgcccc taactccgcc 120 cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg cagaggccga 180 ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg gaggcctagg 240 cttttgcaaa aagctt 256

<210> 20 <211> 293 <212> DNA <213> Homo sapiens <2 2 0> <221> misc_feature <222> (33) <223> n equals a, t, g or c <22 0> <221 > misc_feature <222> (122) <223> n equals a, t, g or c <400> 20 tatacagcct gttagacctg aagatggctc ttnttaaggc caataaggat ctcatttccg 60 cagattgaag gagttcagcg ttctgctgaa tcagcaggtc ttcaatgatc ctttcgtctc 120 tnaagaagac atggtgactg tggtggagga ctggatgaac ttctacatca actattacag 180 gcagcaggtg acaggggagc cccaagagcg agacaaggct ctgcaggagc ttcggcaaga 240 gctgaacact ctggccaacc ctttcctggc caagtacagg gacttcctga agt 293

<210> 21 <211> 272 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (174) <223> n equals a, t, g or c <220> <221> misc_feature < 222> (226) <223> n equals a, t, g or c <40o> 21 atacagcctg ttagacctga aggcagatgg ctctttttaa ggccaataag gatctcattt 60 ccgcagattg aaggagttca gcgttctgct gaatcagcag gtcttcaatg atcctctcgt 120 ctctgaagaa gacatggtga ctgtggtgga ggactggatg aacttctaca tcanctatta 180 caggcagcag gtgacagggg agccccaaga gcgagacaag gctctncagg agcttcggca 240 agagctgaac actctggcca accctttcct gg 272

<210> 22 <2U> 50 <212> DNA <213> Homo sapiens <400> 22 gcagcaggat ccatggctct tcttaaggcc aataaggatc tcatttccgc 50

<210> 23 <211> 36 <212> DNA <213> Homo sapiens <400> 23 gcagcatcta gaggaggagg gcggtgggtg actcgg 36

What Is Claimed Is: 1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: (a) a polynucleotide fragment of SEQ ID NO: 1 or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No: 203571; (b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO: 2 or the cDNA sequence included in ATCC Deposit No: 203571; (c) a polynucleotide encoding a polypeptide domain of SEQ ID NO: 2 or the cDNA sequence included in ATCC Deposit No: 203571; (d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO: 2 or the cDNA sequence included in ATCC Deposit No: 203571; (e) a polynucleotide encoding a polypeptide of SEQ ID NO: 2 or the cDNA sequence included in ATCC Deposit No: 203571 having biological activity; (f) a polynucleotide which is a variant of SEQ ID NO: 1; (g) a polynucleotide which is an allelic variant of SEQ ID NO: 1; (h) a polynucleotide which encodes a species homologue of the SEQ ID NO: 2; (i) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a) - (h), said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or or only T residues. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a mature form or a secreted protein. 3. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding the sequence identified as SEQ ID NO: 2 or the coding sequence included in ATCC Deposit No: 203571. 4. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises the entire nucleotide sequence of SEQ ID NO: 1 or the cDNA sequence included in ATCC Deposit No: 203571. 5. The isolated nucleic acid molecule of claim 2, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus. The isolated nucleic acid molecule of claim 3, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus. 7. A recombinant vector comprising the isolated nucleic acid molecule of claim 1. 8. A method of making a recombinant host cell comprising the isolated nucleic acid molecule of claim 1. 9. A recombinant host cell produced by the method of claim 9. 10 The recombinant host cell of claim 9 comprising vector sequences. An isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: (a) a polypeptide fragment of SEQ ID NO: 2 or the encoded sequence included in ATCC Deposit No: 203571; (b) a polypeptide fragment of SEQ ID NO: 2 or the encoded sequence included in ATCC Deposit No: 203571 having biological activity; (c) a polypeptide domain of SEQ ID NO: 2 or the encoded sequence included in ATCC Deposit No: 203571; (d) a polypeptide epitope of SEQ ID NO: 2 or the encoded sequence included in ATCC Deposit No: 203571; (e) a mature form of a secreted protein; (f) a full length secreted protein; (g) a variant of SEQ ID NO: 2; (h) in allelic variant of SEQ ID NO: 2; or (i) a species homologue of the SEQ ID NO: 2. The isolated polypeptide of claim 11, wherein the mature form or the full length secreted protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus. An isolated antibody that binds specifically to the isolated polypeptide of claim 11. 14. A recombinant host cell expressing the isolated polypeptide of claim 11. 15. A method of making an isolated polypeptide comprising: (a) culturing the recombinant host cell or claim 14 under conditions such that said polypeptide is expressed; and (b) recovering said polypeptide. 16. The polypeptide produced by claim 15. 17. A method of preventing, treating, or ameliorating a medical condition comprising administering to a mammalian subject a therapeutically effective amount of the polynucleotide of claim 1. 18. A method of preventing, treating, or ameliorating a medical condition comprising administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 11. 19. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject related to expression or activity of a secreted protein comprising: (a) determining the presence or absence of a mutation in the polynucleotide of claim 1; (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject related to expression or activity of a secreted protein comprising: (a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample ; (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide. A method of identifying binding partner to the polypeptide of claim 11 comprising: (a) contacting the polypeptide of claim 11 with a binding partner; and (b) determining whether the binding partner effects an activity of the polypeptide. 22. The gene corresponding to the cDNA sequence of SEQ ID NO: 2. A method of identifying an activity in a biological assay, the method comprising: (a) expressing SEQ ID NO: 1 in a cell; (b) isolating the supernatant; (c) detecting an activity in a biological assay; and (d) identifying the protein in the supernatant having the activity. 24. The product produced by the method of claim 23.

Figure 1

Nucleotide and Amino Acid Sequence of BMSP 1

CD-I CD-II *. * 121 TCTGCTGAATCAGCAGGTCTTCAATGATCCTCTCGTCTCTGAAGAAGACATGGTGACTGT 180 21 LLNOOVFNDPLVS EEDMV T ^ 40

CD-II CD-III 181 GGTGGAGGACTGGATGAACTTCTACATCAACTATTACAGGCAGCAGGTGACAGGGGAGCC 240 41 V E D W Μ K F Y I N. Y Y R Q Q V T G E P 60

CD-III CD-IV CD-V

241 CCAAGAGCGAGACAAGGCTCTGCAGGAGCTTCGGCAAGAGCTCAACACTCTGGCCAACCC 30061QE R DKALQELR0 E-LNTLANP80CD VCD VT301TTTCCTGGCCAAGTACAGGGACTTCCTGAAGTCTCATGAGCTCCrGAGTCACCCACCGCC36081FL A KYRDFLKSΗ LPsHPPP100CD E-VII CTCCTCCTAGCTCAGGGACCCAGCCCCTCCTCTCTGAGAAACTCTrGACCTTCATGTCCTT 361 420 101 S S 102 421 480 481 AGGCTGTGCTCCTGCCACTCTACCCTGACACCTCAATAAAGACCAGTGCTGGTTTTGTTG GAAAA 485